Respiratory syncytial virus (RSV) is a leading cause of severe acute lower respiratory tract infection in infants and children worldwide. Bovine RSV (BRSV) is closely related to human RSV and a significant cause of morbidity in young cattle. BRSV infection in calves displays many striking similarities to HRSV infection in humans, and cattle are an outbred population that is naturally susceptible to BRSV infection. Therefore, BRSV infection in calves represents an excellent model for studying RSV infection and antiviral immunity in children. RSV is poorly immunogenic and this has been a complicating factor in the development of a safe and effective RSV vaccine. Polyanhydride nanovaccines have shown great promise as adjuvants and vaccine delivery vehicles in rodent models due to their ability to promote enhanced immunogenicity through both the route of administration and the ability to provide sustained antigen exposure. The experiments in Aim 1 are designed to examine the efficacy of a novel amphiphilic polyanhydride nanoparticle vaccine bearing the recombinant BRSV F and G glycoproteins in a neonatal calf model of RSV infection. Vitamin A deficiency (VAD) is a widespread affliction in infants and young children worldwide. Vitamin A is a critical factor in regulating the immune response and even marginal levels of VAD are associated with impaired immune function and increased susceptibility to respiratory infections, particularly those caused by RSV. Further, VAD has been linked to poor vaccine efficacy. However, despite the strong epidemiologic link between VAD and RSV disease incidence and severity, there exists little experimental evidence for vitamin A in regulating the immune response to RSV infection or vaccination. Therefore, the experiments in Aim 2 will use the model of RSV infection in the calf to determine the role of vitamin A in regulating the immune response to RSV vaccination and infection. Much of our knowledge of RSV infection and immunity stems from studies in rodents and adult animals; however, the experiments proposed here will study a natural host-pathogen interaction and will examine the response in the neonate, the same population commonly targeted by severe disease. It is anticipated that these studies will have a positive impact by identifying a safe and efficacious vaccine for use in children and animals, and by determining the role of vitamin A in the response to both vaccination and infection.